title: A peptide binding to dimerized translationally controlled tumor protein modulates allergic reactions.
abstract: Translationally controlled tumor protein (TCTP) is believed to be involved in a variety of inflammatory processes: secretion of histamine and cytokines such as IL-4, IL-8, IL-13, and granulocyte/macrophage colony-stimulating factor; chemoattraction for eosinophils; augmentation of B cell proliferation; and immunoglobulin production, thereby potentially regulating allergic phenomena. In a previous study, we showed that the cytokine-releasing activity of extracellular TCTP is generated only when TCTP dimerizes via the intermolecular disulfide bond of NH(2)-terminal truncated TCTP implying that the dimerized TCTP (dTCTP) promotes the inflammatory phenomena. Modulation of dTCTP, thus, may offer a strategy for the treatment of chronic allergic diseases. In this study, we searched for dTCTP-binding peptides (dTBPs) by screening a phage-displayed 7-mer peptide library. We identified one peptide in the library, designated as dTBP2, which showed higher affinity to dTCTP than to full-length, monomeric TCTP. dTBP2 inhibited the induction of IL-8 by dTCTP from BEAS-2B cells. dTBP2 also reduced symptom score and eosinophil infiltration in a mouse rhinitis model. This study suggests that the dTBP2 binding to dTCTP modulates the release of inflammatory mediators of dTCTP. This result may provide a rational strategy for the treatment of allergic diseases.
authors.affiliation: College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, South Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Kim
authors.forename: Junho
authors.initials: J
authors.lastname: Chung
authors.forename: Chulhee
authors.initials: C
authors.lastname: Lee
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Jung
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.forename: Kyunglim
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D001435:Bacteriophages / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000378:metabolism*; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D010455:Peptides; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1